This is a proposal to participate as a collaborative center in a randomized double blind clinical trail of oral or transdermal estrogen replacement therapy, given with or without a progestin, vs oral or transdermal placebo in 150 postmenopausal women. Subjects will be recruited from the UCSD Menopause Clinic, private and University physicians, and by media advertising. Eligibility requirements include age 40-55 years, not more than 3 years post-menopause with confirmatory FSH levels, and no previous estrogen replacement therapy. Life-threatening conditions and diseases which distort bone metabolism will be exclusionary criteria, but most other conditions (including the presence of a uterus) will not be, so that the trial results will be generalizable to more post-menopausal women. Most endpoints of interest will be either cardiovascular risk factors or markers for bone metabolism and osteoporosis (bone density), and will be measured twice a year throughout the study. These endpoints include body mass index, blood pressure, lipids, lipoproteins, apolipoproteins, fasting glucose and tolerance, clotting/coagulation factors, selected minerals, calcitonin and bone density. In addition, general well being, relief of menopausal symptoms (if any) and depression score will be monitored. Possible untoward effects, primarily gallstones and endometrial cancer, will be monitored by a local gynecology advisory board, with endometrial biopsy as indicated, and by the collaborative safety and data monitoring board. Covariates of interest, because they may impact on the endpoints above, will be measured at baseline and throughout, and include liver and renal function tests, cigarette smoking, alcohol use, exercise, nutrition supplements and medication use, reproductive and medical history, family history of heart disease and osteoporosis, serum vitamin D, and attitudes about menopause.